Elucidating the impact of alcohol on the adolescent brain is of paramount importance not only to understand the nature of the addictive process but also to prevent the progression from casual alcohol use to dependency. The overall goal of this proposal is to test the hypothesis that the adolescent brain is uniquely susceptible to physiological changes induced by ethanol and that these ethanol-induced perturbations during adolescence persist into adulthood rendering the animals more vulnerable to its addicting effects. Specifically, we propose that ethanol exposure during adolescence alters key neuronal circuitry and that these changes persist into adulthood with consequent changes in the normal functions of this pathway that may be responsible for the predisposition of the "ethanol-exposed" brain to ethanol use as compared to the "ethanol-naive" brain. The proposed experiments are designed to determine sex differences in the long-term effects of chronic exposure to experimenter administered ethanol (or saline) during adolescence [postnatal day (PND) 30-50] or adulthood (PND 60-80) in male and female rats. Following ethanol (or saline) exposure, adolescent-exposed and adult- exposed rats will be tested as adults (PND 74 or PND 104, respectively) for the effects of ethanol preexposure on ethanol consumption via voluntary sweetened ethanol intake (Specific Aim 1). For a neurochemical measure, ethanol-induced dopaminergic responses of the nucleus accumbens septi, likely to be affected and involved sequentially in the progression from alcohol use to alcohol dependency, will be measured in response to experimenter-administered ethanol (0.75, 1.75 g/kg/ip ethanol) or saline using in vivo microdialysis (Specific Aim 2). Blood and brain ethanol concentrations will be examined in all proposed experiments to determine possible sex and pretreatment differences in the metabolism of ethanol. Additionally, estrous cycling will be evaluated in all females during adulthood to investigate the effects of changes in the estrous cycle on long term behavioral and neurochemical consequences of chronic ethanol exposure during adolescence or adulthood. Results from these studies will clearly delineate the lasting impact of chronic exposure to ethanol during adolescence as compared to adulthood on the subsequent adult brain and behavior. Information on the alteration of ethanol consumption patterns and neurochemical processes of the brain that render animals susceptible to ethanol addiction is critically important for understanding the addictive process and how it may be prevented or treated. PUBLIC HEALTH RELEVANCE: These studies will examine the long term effects of ethanol on the adult male and female brain and behavior following ethanol exposure during adolescence or adulthood.